Fundamental Investigations of Muscle Cell Interactions for Engineering 'Living Diodes'

PI：Zorlutuna，Pinar 提案编号：1403546机构：康涅狄格大学题目：肌细胞相互作用的基础研究工程'活二极管'生物计算是一个新兴的领域，旨在使用生物成分进行信号处理。肌肉细胞，是电和机械反应，是有前途的候选人，这种新的方法来处理信息。使用基于肌细胞的活机电电路元件实现受控和可靠的定向信号流可以改变生物电和生物力学接口的设计方式，并影响基础科学和生物工程应用。拟议的研究将导致更好地了解肌肉细胞网络中的细胞-细胞和细胞-环境通信，影响潜在的未来应用，从生物机器人和人机界面到了解和治疗肌肉退行性疾病和心律失常的生物工程方法。这些进步将解决重要的社会问题，如肢体丧失和心脏病。 除了专业出版物和与本研究相关的拟议共同组织的会议研讨会之外，还计划为大学，高中和中学的学生和教师开展教育和宣传活动。 该奖项由两个项目共同颁发。(1)生物医学工程，在化学，生物工程，环境和运输系统司（工程局）;（2）生物基础设施司生物研究仪器开发（生物科学理事会）。该项目的目标是研究一种新型二极管的特性，这种二极管由可兴奋的肌肉细胞和不可兴奋的成纤维细胞的新型组合制成，然后研究这些细胞类型之间更复杂的相互作用，这些细胞被组织成逻辑门，最终成为机电电路。为了实现这一目标，该提案测试了特定的假设，即这两种细胞类型的非均匀排列可以被设计为允许信号在可兴奋到不可兴奋的方向上传播，但不是相反。第一个研究目标是研究微图案化的肌肉细胞的二极管样行为，使用单细胞机械和单细胞电刺激与独特组合的微电极阵列，三维荧光和原子力显微镜的电，光/化学和机械询问的单个细胞，或细胞群体，限于限定的几何形状。第二个研究目标是研究各种微图案化的几何形状和可兴奋/不可兴奋细胞组合的比例，以研究信号传播的基本特性，最终设计逻辑门模拟物的明确目标。拟议的研究将为开辟一个新的领域铺平道路，其中基于肌肉细胞的结构可用作电路元件，随后用作生物电和生物力学接口，并作为人工生物系统的控制单元，具有生物计算应用和人/机接口的明确潜在机会。

PI: Zorlutuna, Pinar Proposal Number: 1403546Institution: University of ConnecticutTitle: Fundamental Investigations of Muscle Cell Interactions for Engineering 'Living Diodes'Biocomputing is an emerging field that aims to use biological components for signal processing. Muscle cells, being both electrically and mechanically responsive, are promising candidates for this new approach to information processing. Achieving controlled and reliable directional signal flow using muscle cell-based living electromechanical circuit elements can transform how bioelectrical and biomechanical interfaces are engineered, and impact both fundamental science and bioengineering applications. The proposed research will lead to a better understanding of cell-cell and cell-environment communication in muscle cell networks, impacting potential future applications ranging from biorobotics and human-machine interfaces to bioengineering approaches for understanding and treating muscular degenerative disorders and cardiac arrhythmia. Such advancements will address socially important problems, such as limb loss and heart diseases. Beyond professional publications and a proposed co-organized conference symposium related to this research, educational and outreach activities are planned for university, high school, and middle school students and teachers. This award is being made jointly by two Programs. (1) Biomedical Engineering, in the Chemical, Bioengineering, Environmental and Transport Systems Division (Engineering Directorate); and (2) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate).The goal of this project is to examine the properties of a new type of diode, made from a novel combination of excitable muscle cells and non-excitable fibroblast cells, and then study more complex interactions between these cell types that are organized to function as logic gates and eventually as electromechanical circuits. To achieve this goal, this proposal tests the specific hypothesis that a non-uniform arrangement of these two cell types can be engineered to allow signal propagation in the excitable to non-excitable direction, but not the reverse. The first research objective is to study diode-like behavior of micropatterned muscle cells using single-cell mechanical and single-cell electrical stimulation with uniquely combined microelectrode arrays, 3-dimensional fluorescence, and atomic force microscopy for electrical, optical/chemical, and mechanical interrogation of individual cells, or populations of cells, confined to defined geometries. The second research objective is to study various micropatterned geometries and ratios of excitable/non-excitable cell combinations to investigate the fundamental properties of the signal propagation, with the explicit goal of ultimately engineering logical gate analogues. The proposed research will pave the way for opening up a new field in which muscle cell-based structures can be used as circuit elements that subsequently serve as bioelectrical and biomechanical interfaces, and as control units for artificial bio-systems with clear potential opportunities for biocomputing applications and human/machine interfaces.